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MINISTRY OF TRAINNING AND EDUCATION MINISTRY OF NATIONAL DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES - VU THANH LAM RESEARCH THE MYOCARDIAL PROTECTIVE AND HEMODYNAMIC EFFECTS OF SEVOFLURANE AND PROPOFOL IN PATIENTS UNDERGOING OPEN CARDIAC SURGERY UNDER CARDIOPULMONARY BYPASS Specialty: ANESTHESIOLOGY Code: 62720122 ABSTRACT OF PHD THESIS Hanoi – 2022 THE THESIS WAS DONE IN: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Scientific instructors: Prof PhD Nguyen Quoc Kinh Ass Prof PhD Nguyen Minh Ly Reviewer 1: Reviewer 2: Reviewer 2: This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year The thesis can be found at: National Library of Vietnam Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences Central Institute for Medical Science Infomation and Tecnolo INTRODUCTION Open cardiac surgery under cardiopulmonary bypass (CPB) is a common surgery in the world as well as in Vietnam This is a complicated surgery with many potential complications, in which the myocardium is damaged by many causes leading to myocardial ischemia, myocardial infarction (MI), myocardial dysfunction, low cardiac output syndrome (LCOS), Therefore, many measures have been put in place to protect the myocardium, in which the selection of safe anesthetic drugs that have little effect on cardiovascular function is given priority Many studies have shown that sevoflurane has a myocardial protective effect through mechanisms of ischaemic preconditioning, while propofol also has the ability to protect the myocardium against physical damage due to its increased ability to tissue antioxidant and anti-apoptotic properties Therefore, these are the two main drugs used to anesthetize patients undergoing open cardiac surgery under CPB And it is important to find out which drugs are more protective of the myocardium This issue has been interested by researchers around the world and Vietnam for many years, but so far there is no consensus on which drug is more beneficial In Vietnam, no studies have been conducted to compare of the myocardial protective effect of total anesthesia with sevoflurane versus propofol in patients undergoing open cardiac surgery under CPB Therefore, this study was conducted with two objectives: Comparison of the myocardial protective effect between total anesthesia with sevoflurane versus propofol in patients undergoing open cardiac surgery under cardiopulmonary bypass Evaluation of changes in some hemodynamic indices and early postoperative results in these patients THE NEW CONTRIBUTION OF THE THESIS Total inhalation anesthesia with sevoflurane has a better myocardial protective effect than total intravenous anaesthesia with propofol: The heart beats faster on its own and requires less pacemaker after aortic unclamping; plasma concentrations of CK-MB at hours, 24 hours, 48 hours and plasma concentration of hs-troponin T at 24 hours after surgery, the need for inotropes and vasopressors during and after surgery of the sevoflurane group were lower than those of the propofol group (p < 0.05) Compared with total propofol anesthesia, total anesthesia with sevoflurane had less hypotension during induction of anesthesia (67.9% vs 96.4%) and had a higher ScvO2 after aortic unclamping (78.7 ± 8.5% vs ± 13.5%) but did not differ in early postoperative outcomes (duration of mechanical ventilation, length of ICU stay and length of hospital stay, rates of complication and mortality within 30 days after surgery) THE STRUCTURE OF THE THESIS The reseach consists of 143 pages: pages of introduction, 39 page of overview, 24 pages of subjects and methods, 31 pages of research results, 45 pages of discussion, page of conclusions and page of suggestion, 44 tables, 19 figures, charts; the reserch consist of 155 references (23 sources in Vietnamese and 132 sources in English) Chapter – OVERVIEW 1.1 Some problems with surgery, cardiopulmonary bypass (CPB) and anesthesia for open cardiac surgery under CPB 1.1.1 Brief history of open cardiac surgery under CPB On May 6, 1953, for the first time, the first open cardiac surgery under CPB was successfully performed in humans by Gibbon at Massachusetts General Hospital in Boston to patch the atrial septal defect In Vietnam, on May 5, 1965, Professor Ton That Tung was the first person to successfully patch the atrial septal defect at Viet Duc Hospital Today, with the advancement of anesthesia, open cardiac surgery under CPB has been able to treat many complex heart diseases 1.1.2 Cardiopulmonary bypass (CPB) 1.1.2.2 Effects of CPB CPB affects the normal reflexes and chemoreceptors of the circulatory system and many other disorders such as: Coagulation disorders, blood cell activation, complement and kallikrein - kinnin activation causing increased vascular permeability, fluid balance disorder and edema, strong neuroendocrine response to stress, increased secretion of catecholamines, cortisol, glucagon , release of messenger proteins, cytotoxins and vasoconstrictors, produce microcirculation, venous many substances that pressure increases, plasma block the osmolality decreases Organizations and organs suffer from local ischemia, increased interstitial fluid, increased cytotoxic substances that damage cells Ischemia and reperfusion increase damage to the heart and other organs 1.1.3 Anesthesia for open heart surgery under CPB Open cardiac surgery under CPB was under general anesthesia, endotracheal intubation, command respiration and CPB Intravenous or respiratory anesthetic or a combination of both drugs can be used for anesthesia during open cardiac surgery under CPB 1.2 Myocardial injury during open cardiac surgery under CPB 1.2.2 Mechanisms of myocardial injury during open cardiac surgery under CPB The mechanisms of myocardial injury during open cardiac surgery under CPB are multifactorial and include those due to early graft failure (graft occlusion, graft kinking or overstretching, subtotal anastomotic stenosis, or graft spasm) and those due to non-graft mechanisms include acute global ischaemia/reperfusion injury induced by aortic crossclamping and declamping, systemic inflammatory injury from CPB, distal coronary microembolization, surgical manipulation of the heart, particulate and soluble factors released from surgically manipulated coronary vessels, genetic susceptibility, In which, acute global ischaemia/reperfusion injury is very important Myocardial ischemia of limited duration (< 20 min) results in functional recovery and there is no evidence of structural damage or biochemical evidence of tissue damage However, if myocardial ischemia lasts longer, it will lead to irreversible myocardial damage and myocardial cells die 1.3 Methods of myocardial protection during open cardiac surgery under CPB 1.3.1 Myocardial protection with cardioplegic solution The principle of myocardial protection is to increase myocardial oxygen supply and decrease its oxygen demand Crystalloid or blood cardioplegic solutions or new solutions such as Custodiol,…can be used 1.3.2 Endogenous therapeutic strategies for myocardial protection These strategies work by training the myocardium to adapt to ischemic stress by subjecting it to brief non-lethal episodes of ischaemia and reperfusion, helps the myocardium to avoid the harmful effects of ischemia-reperfusion phenomenon and reduces the size of the MI area 1.3.3 Hypothermia This strategy decreases myocardial injury to ischemia in the period of CPB The mechanism is a decrease in oxygen consumption caused by decreased cellular metabolic activity and enzymatic reactions 1.3.4 Pharmacological strategies for myocardial protection These strategies use drugs with different myocardial protection effects such as beta-adrenergic antagonists, acadesine, pexelizumab, statins, etc 1.4 Role of sevoflurane and propofol in myocardial protection and hemodynamic effects 1.4.1 Sevoflurane Sevoflurane is an ethyl propyl ether, belonging to the group of halogenated respiratory anesthetics with myocardial protection effects based on the mechanisms of ischaemic preconditioning, ischaemic postconditionning and effects on the inflammatory response On the cardiovascular system, sevoflurane inhibits myocardial contractility very slightly, causing no increase in heart rate, insignificant decrease in CO, slight decrease in peripheral resistance, cause less hypotension, and reduction in myocardial oxygen consumption, reducing coronary resistance but no evidence for a coronary steal phenomenon at MAC 0-2 1.4.2 Propofol Propofol (2-6-di-isopropyl phenol) is an intravenous anesthetic which has the ability to protect the myocardium against cardiac damage due to increased tissue antioxidant through inhibition of plasma membrane Ca2+ channels, increasing myocardial proteinkinase C activity, and antiapoptotic properties On the cardiovascular system, propofol causes a decrease in systolic and diastolic blood pressure by direct effects on both the venous and arterial systems When induction of anesthesia with propofol, blood pressure may decrease by 20-30% corresponding to increased drug concentration in the blood Propofol has little effect on heart rate, cause a moderate decrease in CO 1.5 Researches at home and abroad on myocardial protection and hemodynamic effects of sevoflurane and propofol in patients undergoing open cardiac surgery under CPB 1.5.1 Researches at abroad In patients undergoing congenital cardiac surgery, Malagon et al (2005) found no difference in troponin T concentrations within the first 24 hours after surgery between the sevoflurane and propofol groups For patients undergoing valvular surgery under CPB, researches by Cromheecke et al (2006), Yang et al (2017) found that total anesthesia or maintenance anesthesia with sevoflurane has a good myocardial protection effect (decreased cardiac enzymes, inflammatory markers, higher rate of spontaneous heart beat), more stable hemodynamics (higher CO, reduced inotropic and vasopressor requirements) than propofol anesthesia In contrast, a research by Bignami et al (2012) of 100 patients found that patients with coronary artery disease undergoing mitral valve surgery did not benefit from the cardioprotective properties of sevoflurane that used for maintenance anesthesia before and after CPB 1.5.2 Researches at home The researches by Ho Thi Xuan Nga et al (2011) in patients undergoing CABG, Le Huu Dat et al (2012) in patients undergoing heart valve surgery showed that sevoflurane used continuously after induction of anesthesia with propofol reduced electric shock rate after aortic unclamping, cardiac enzymes and need for inotropes and vasopressors compared with propofol TIVA, but no difference in other outcomes In summary, the researches were mainly conducted in patients undergoing CABG, there are some researches in patients undergoing valvular surgery but the damage is due to degeneration, unlike in Vietnam it is caused by rheumatic heart disease so anesthetics may have different effects Furthermore, the researches were heterogeneous in design Chapter - SUBJECTS AND METHODS 2.1 Research subjects 2.2.1 Selection criteria Patients (≥18 years) who are indicated for open cardiac surgery under CPB are prepared for the following types of surgery: Replace or repair cardiac valve, replace or repair cardiac valve in combination with Maze procedure or patching the septal defect, patch the atrial septal defect, ventricular septal defect 2.2.2 Exclusion criteria Disagree with study; unstable angina; coronary stenosis; myocardial infarction < weeks; LVEF < 30%; preoperative inotropic, vasopressor, or balloon therapy; severe COPD; ALT/AST > 150 U/l; blood creatinine > 130 µmol/l; history of neurological or psychiatric disorders; contraindications to sevoflurane, propofol; history of cardiac surgery; family history of elevated Malignant hyperthermia in surgery 2.1.3 Criteria for taking out of the research Complications in anesthesia, CPB or surgery, disagree to continue the study, did not collect enough data, re-operated 2.2 Reseach methodology 2.2.1 Research design A single-blind, randomized controlled clinical intervention study 2.2.2 Sample size and sampling method Sample size: Apply the formula for comparison of two means: n 2c 2 1 Calculated n = 22.79 or approximately 23 patients for each group Sampling method: Randomized into groups: + Group P: Total intravenous anesthesia (TIVA) with propofol + Group S: Total inhalation anesthesia with sevoflurane 2.2.3 The main assessment criteria for the research 2.2.3.1 Objective 1: Compare the myocardial protection effect between the two groups *Clinical: - Characteristics of the heart beating again after aortic unclamping: + Percentage of patients with the heart beats again on its own and electric shock after aortic unclamping + Duration of the heart beating again after aortic unclamping, duration of weaning of cardiopulmonary bypass + Percentage of patients with sinus rhythm, using a pacemaker after aortic unclamping - Need for inotropes and vasopressors during and after surgery: + Percentage of patients requiring inotropes and vasopressors, percentage of type of inotropes and vasopressors using during and after surgery + The average number of inotropes and vasopressors per patient must be used during and after surgery + Amount and duration of inotropes and vasopressors used during and after surgery + Vasoactive-inotropic score after surgery *Subclinical: - Cardiac enzymes (hs-Troponin T, CK-MB, NT-proBNP), hs-CRP before and after surgery hours, 24 hours, 48 hours - Postoperative transthoracic echocardiography: EF (%) according to Simpson method performed by cardiac sonographers and cardiologist at hours after surgery and before hospital discharge 2.2.3.2 Objective 2: Evaluate changes in some hemodynamic indices and early results after surgery *Hemodynamic index: 11 *Management of unstable hemodynamics: - Hypotension after induction of anesthesia: Trendelenburg position 30 degrees + ephedrine mg every minutes to maintain MAP ≥ 65 mmHg - Indications for the use of dobutamine: MAP < 65 mmHg, enough preload (CVP > 12 mmHg but MAP does not increase by 10 mmHg at Trendelenburg position 30 degrees), signs of low CO (ScvO2 < 70% or blood lactate > mmol/l and urine < 0.5 ml/kg/hour or poor myocardial contractility before chest closure) - Indications for the use of noradrenaline: MAP < 65 mmHg without signs of low CO or hypovolaemia (ScvO2 ≥ 70% or EtCO2 is normal when ventilation is not changed and little changes of MAP in Trendelenburg position) - Infusion (gelofunsine): Bolus doses of ml/kg over 15 minutes (or red blood cells if Hb < 10 g/dl) if MAP < 65 mmHg with signs of hypovolaemia (MAP increase > 10 mmHg at Trendelenburg position, CVP < mmHg, with invasive blood pressure fluctuations according to mechanical ventilation) 2.2.8 Data analysis By medical statistics algorithm with SPSS 26.0 software Chapter - FINDINGS 3.1 Characteristics of the study patients, characteristics of anesthesia, surgery and CPB The study included 56 patients from April 2016 to May 2018 Each group has 28 patients The mean age was 49.8 ± 13.2 There was no significant difference in age, sex, height, weight, BMI, preoperative status according to ASA, NYHA, ECG, heart/thoracic index, pulmonary artery pressure, LVEF, EuroSCORE, risk factors and comorbidities as well as subclinical features and the amount of midazolam, fentanyl, muscle 12 relaxants used during anesthesia, surgical methods, duration of anesthesia, surgery, CPB and aortic clamping, amount of blood and fluid transfused during surgery (p > 0.05) 3.2 Characteristics of myocardial protection effects of the two groups 3.2.1 Clinical features 3.2.1.1 Characteristics of the heart beating again after aortic unclamping Table 3.11 Characteristics of the heart beating again after aortic unclamping Group Group S (n = 28) Group P (n = 28) n (%) n (%) Heart beats again on its own 25 (89.3) 23 (82.1) > 0.05 Electric shock (10.7) (17.9) > 0.05 Sinus rhythm 23 (82.1) 16 (57.1) < 0.05 Using a pacemaker (25.0) 15 (53.6) < 0.05 Characteristics p The proportion of patients with sinus rhythm after aortic unclamping of the sevoflurane group was higher than that of the propofol group (p < 0.05) The percentage of patients who had to use a pacemaker after aortic unclamping of the sevoflurane group was lower than that of the propofol group (p < 0.05) Table 3.12 Duration of the heart beating again after aortic unclamping and duration of weaning of cardiopulmonary bypass Group Group S (n = 28) Group P (n = 28) p Duration ( X SD) ( X SD) The heart beating again (second) 83.2 75.4 153.1 127.7 < 0.05 Weaning of CPB (minute) 16.3 ± 6.7 18.1 ± 6.5 > 0.05 13 Duration of the heart beating again after aortic unclamping of the sevoflurane group was lower than that of the propofol group (p < 0.05) 3.2.1.2 Need for inotropes and vasopressors during and after surgery Table 3.13 Need for inotropes and vasopressors during and after surgery Group Parameter Group S Group P (n = 28) (n = 28) p type of drugs n (%) 10 (35.7) 12 12 (42.9) 22 types of drugs n (%) (7.1) (42.9) 10 (35.7) (78.6) Number of drugs/ patient ( X SD) (medicine) 0.50 ± 0.64 1.14 ± 0.76 < 0.01 < 0.01 The proportion of patients using inotropes and vasopressors, the average number of inotropes and vasopressors per patient of the sevoflurane group was lower than those of the propofol group (p < 0.01) Table 3.14 Use dobutamine, noradrenalin during and after surgery Group Group S Group P (n = 28) (32.1) 20 (71.4) < 0.01 168.25 406.54 401.56 ± 424.42 < 0.05 10.1 23.3 20.9 22.3 > 0.05 (17.9) 12 (42.9) < 0.05 Amount of drug (mg) 0.48 ± 1.40 0.91 ± 1.68 > 0.05 Duration ( X SD) (h) 3.6 10.8 4.3 9.1 > 0.05 n (%) Amount of drug (mg) Duration ( X SD) (h) n (%) in Dobutamin Noradrenal p (n = 28) Parameter The proportion of patients using dobutamine, noradrenaline and the amount of dobutamine using during and after surgery of the sevoflurane group was lower than those of the propofol group (p < 0.01 or 0.05) 14 Table 3.16 The maximum VIS indexes after surgery Group Group S Group P Time p (n = 28) ( X SD) (n = 28) ( X SD) H6 1.34 ± 2.70 5.89 ± 5.74 < 0.01 H24 1.88 ± 3.18 6.37 ± 5.73 < 0.01 H48 2.23 ± 3.24 6.37 ± 5.73 < 0.01 p > 0.05 > 0.05 The maximum VIS indexes within hours, 24 hours and 48 hours after surgery of the sevoflurane group was lower than those of the propofol group (p < 0.01) Table 3.17 The maximum VIS indexes after surgery in the group of patients using inotropes and vasopressors Group Group S Group P (n = 12) ( X SD) (n = 22) ( X SD) p H6 3.13 ± 3.44 7.50 ± 5.45 < 0.05 H24 4.38 ± 3.60 8.11 ± 5.24 < 0.05 H48 5.21 ± 2.97 8.11 ± 5.24 < 0.05 p > 0.05 > 0.05 Time The maximum VIS indexes within hours, 24 hours and 48 hours after surgery in the group of patients who had to use inotropes and vasopressors of the sevofluran group was lower than those of the propofol group (p < 0.05) 3.2.2 Subclinical features 3.2.2.1 Changes in cardiac enzyme after surgery 15 Table 3.18 Plasma CK-MB before and after surgery Group S (n = 28) Group P (n = 28) ( X SD) (ng/ml) ( X SD) (ng/ml) T0 1.50 0.86 1.61 0.60 > 0.05 H6 55.84 30.61 74.24 35.00 < 0.05 H24 26.77 16.78 42.14 28.26 < 0.05 H48 6.49 3.39 9.89 6.41 < 0.05 p < 0.01* < 0.01* Group Time p Note: (*) - Compare the same group between the two time points: before - after Plasma CK-MB after surgery hours (H6), 24 hours (H24) and 48 hours (H48) of the sevoflurane group was lower than those of the propofol group (p < 0.05) Table 3.19 Plasma hs-troponin T before and after surgery Group S (n = 28) Group P (n = 28) Group Time p ( X SD) (ng/ml) ( X SD) (ng/ml) T0 0.01 0.01 0.01 0.01 > 0.05 H6 1.28 1.34 1.63 1.50 > 0.05 H24 0.88 0.89 1.54 1.35 < 0.05 H48 0.62 0.61 0.96 0.78 > 0.05 p p* < 0.01 p# > 0.05, p† < 0.01 Note: (*) - Compare the same group S between the two time points: before - after; (#) – Compare the same group P between H6 and H24; (†) – Compare the same group P between the two time points in the time points: T0, H6 (or H24) and H48 16 Plasma hs-troponin T after surgery 24h (H24) of the sevoflurane group was lower than that of the propofol group (p < 0.05) 3.3 Evaluate changes in some hemodynamic indices and early results after surgery 3.3.1 Evaluate changes in some hemodynamic indices 150 *p < 0.05 mmHg 100 (*) (*) T3 T4 Time MAP Sevoflurane T5 (*) 50 T0 T1 T2 H6 H24 H48 MAP Propofol Chart 3.6 Change in mean arterial blood pressure over time The systolic, diastolic and mean blood pressure during surgery at the time points immediately before CPB (T3), 15 minutes after CPB (T4) and the end of surgery (T5) of the propofol group was lower than those of the % sevoflurane group (p < 0.05) *p < 0.05 100 80 60 40 20 (*) Ta Tb H6 Time Group S Group P Chart 3.7 Change of ScvO2 over time H24 17 ScvO2 after aortic unclamping of the propofol group was lower than that of the sevoflurane group (p < 0.05) Table 3.31 The proportion of patients and amount of ephedrine used at induction of anesthesia and during cardiopulmonary bypass Group Parameter Induction of anesthesia Cardiopulmonary bypass n (%) Amount of drug X SD (mg) n (%) Amount of drug X SD (mg) Group S Group P (n = 28) (n = 28) 19 (67.9) 27 (96.4) < 0.01 15.0 ± 12.0 25.0 ± 7.5 < 0.01 27 (96.4) 26 (92.9) > 0.05 45.4 35.0 50.5 37.1 > 0.05 p The proportion of patients and amount of ephedrine used at induction of anesthesia of the sevoflurane group was lower than those of the propofol group (p < 0.01) 3.3.2 Some early results after surgery The proportion of patients requiring blood transfusion and the amount of required blood after surgery; duration of mechanical ventilation, ICU stay and hospital stay; percentage of complications and mortality within 30 days after surgery of the two groups were not significantly different with p > 0.05 Chapter - DISCUSSION 4.1 Characteristics of the study patients, characteristics of anesthesia, surgery and cardiopulmonary bypass The two study groups had no statistically significant differences in age, gender, height, weight, BMI, preoperative status according to ASA, NYHA, ECG, heart/chest index, pulmonary artery pressure, LVEF, 18 EUROSCORE, comorbidities, subclinical features, duration of anesthesia, surgery, CPB and aortic clamping and the amount of midazolam, fentanyl, muscle relaxants used during anesthesia To assess the depth of anesthesia of the sevoflurane group, we used the drug's minimum alveolar concentration – MAC According to the European Society of Cardiothoracic Surgery/European Society of Thoracic Anesthesiology/European Board of Cardiovascular Transfusion (2019), the MAC range from 0.7 to 1.3 of sevoflurane was not significantly different from BIS (40 to 60) on the awareness of surgery as well as the need to use drugs between the two groups On the other hand, studies also show to protect the myocardium effectively MAC must be ≥ 0.75 So in this study, we used sevoflurane with MAC from 0.8 to 1.2 to ensure the depth of anesthesia as well as the myocardial protection effects To assess the depth of anesthesia of the propofol group, we used targetcontrolled infusion (TCI) anesthesia According to a study by Nguyen Van Cuong et al (2020) in patients undergoing valvular heart surgery under CPB, Ce propofol at the time of loss of consciousness at induction of anesthesia was 1.9 μg/ml and then entropy (RE, SE) always in the range of 40 to 60 with Ce propofol 2.8 to 3.7 μg/ml On the other hand, studies have shown that continuous infusion of propofol 60 to 120 μg/kg/min (Ce 2.7 to 5.4) in patients undergoing open cardiac surgery was associated with a reduction in biomarkers of cardiac injury Therefore, administer propofol under TCI anesthesia with the start of Ce at 1.5 μg/ml and increase 0.5 μg/ml every two minutes until loss of consciousness (loss of verbal contact, loss of eyelid reflex), then maintain Ce to μg/ml to ensure the depth of anesthesia as well as the myocardial protection effects In summary, the general characteristics of the study patients, the characteristics of anesthesia, surgery and CPB of the two study groups 19 were not statistically significant That proves the homogeneity of the objects participating in the study and randomization into two groups 4.2 Myocardial protection effects of the two groups Evaluation of the myocardial protection effect of anesthetics based on clinical criteria such as characteristics of the heart beating again after aortic unclamping, need for inotropes and vasopressors during and after surgery as well as subclinical criteria such as changes in cardiac enzymes, inflammatory markers, and left ventricular ejection fraction (EF Simpson) after surgery In particular, the change of troponin and CK-MB is a reliable assessment method to confirm the myocardial protection effect of used anesthetics based on two groups with the same physical characteristics and the same characteristics about surgery, CPB and other drugs used during anesthesia, surgery as well as are reasonably designed to ensure the depth of anesthesia and the myocardial protection effect of the drugs In the design of this study, we used MAC 0.8 to 1.2 in combination with MAP to adjust concentrations of sevoflurane and Ce to μg/ml in combination with MAP to adjust the propofol infusion rate to suit each stage as well as the patient's condition during surgery and is also consistent with studies around the world on ensuring the depth of anesthesia and the myocardial protection effect of the drug No anesthesia awareness occurred in either group, indicating that it is reasonable to use sevoflurane with MAC 0.8 to 1.2 and propofol with Ce to μg/ml The study results in Tables 3.18 and 3.19 showed that plasma concentrations of CK-MB and hs-troponin T of the two groups increased after surgery However, plasma concentrations of CK-MB after surgery hours, 24 hours, 48 hours and plasma concentrations of hs-troponin T after surgery 24 hours of the sevoflurane group were lower than those of the propofol group (p < 0.05) This shows that total anesthesia with 20 sevoflurane is effective in reducing myocardial damage compared with total anesthesia with propofol These results are similar to those of the authors: Cromheecke et al (2006) in patients undergoing aortic valve replacement, Yang et al (2017) in patients undergoing heart valve replacement The authors found that sevoflurane anesthesia is effective in reducing plasma concentrations of cardiac enzymes (troponin, CK-MB) after surgery compared with propofol anesthesia However, our study results are different from Bignami et al (2012) when studying in patients undergoing mitral valve surgery on patients with coronary artery disease In this study, the authors did not find difference in myocardial protection effect between sevoflurane and propofol The reason may be that the author did not use sevoflurane during the induction of anesthesia and CPB in the group of respiratory anesthesia, so it may affect the ischaemic preconditioning While, in our study, both sevoflurane and propofol were administered during anesthesia and surgery, that may provide optimal myocardial protection In addition, the myocardial protection effect of sevoflurane and propofol may be related to the used drug concentrations Experimental studies have shown that MAC of inhaled anesthetics has a beneficial effect on myocardial injury, concentrations below 0.75 MAC usually have no effect, while concentrations > 1.5 MAC not lead to more effective protection In our study, we maintained sevoflurane at MAC 0.8 to 1.2 In addition, the myocardial protection effect of anesthetics is also based on the characteristics of the heart beating again after aortic unclamping and the need for inotropes and vasopressors during and after surgery In our study, the total anesthesia group with sevoflurane had the duration of the heart beating again and the proportion of patients who had to use a pacemaker after aortic unclamping, the percentage of patients 21 who had to use inotropes and vasopressors (dobutamine and noradrenalin) and the amount of dobutamine used during and after surgery were lower than those of the total anesthesia group with propofol with p < 0.05; the average number of inotropes and vasopressors per patient had to use during and after surgery, the maximum VIS indexes within hours, 24 hours and 48 hours after surgery were significantly lower than those of the total anesthesia group with propofol with p < 0.01 (< 0.05 for the group using inotropes and vasopressors) This indicated faster heart rate recovery and less myocardial dysfunction in the total anesthesia group with sevoflurane compared with the propofol group This results are similar to the research results of Yang et al (2017) However, left ventricular ejection fraction (LVEF) before and after surgery of the two study groups was not statistically significant different with p > 0.05 The results of our study are similar to those of Le Huu Dat et al (2012) when studying in patients undergoing valvular surgery about left ventricular ejection fraction before discharge In summary, sevoflurane has advantages than propofol in protecting myocardium in patients undergoing open cardiac surgery under CPB 4.3 Evaluate changes in some hemodynamic indices and early results after surgery 4.3.1 Evaluate changes in some hemodynamic indices during and after surgery Evaluation of the hemodynamic effects of anesthetics is based on the evaluation of the effects of anesthetics on basic hemodynamic parameters such as heart rate, arterial blood pressure, central venous pressure as well as the indices about cardiac output (CO), systemic vascular resistance, need for inotropes, vasopressors during and after surgery, In addition, the role of central venous oxygen saturation (ScvO2) is very important to 22 assess hemodynamic status It is an important parameter for determining an adequate supply of oxygen and CO The results of the above study showed that the hemodynamics of the two study groups were maintained relatively stable during and after surgery under the effect of inotropes and vasopressors Although the propofol group had systolic, diastolic and mean blood pressure just before CPB, 15 after CPB and the end of surgery were significantly lower than those of the sevoflurane group but these blood pressure values were still within the target range and within the normal range Furthermore, the propofol group also had lower ScvO2 after aortic unclamping, the need for ephedrine to raise blood pressure during induction of anesthesia as well as the need for for inotropes and vasopressors during and after surgery were generally significantly higher than those of the sevoflurane group Thus, total anesthesia with sevoflurane has more stable hemodynamics than total anesthesia with propofol As well as the myocardial protection effect, the use of different methods of anesthesia will have different hemodynamic effects Le Huu Dat et al (2012) when studying in patients undergoing heart valve surgery found that sevoflurane used continuously after induction of anesthesia with propofol had the effect of reducing significantly the rate of using ephedrine in surgery and the duration of used inotropic compared with the total anesthesia group with propofol but heart rate, blood pressure, central venous pressure, rates of using noradrenaline and dobutamine were not different between the two groups The reason our study results and the author's are different from the hemodynamic effects of the two drugs are due to our method of anesthesia and research object being different from the author's as analyzed above Also in patients undergoing valvular surgery, Yang et al (2017) found that the group receiving 23 continuous sevoflurane after induction of anesthesia with midazolam, fentanyl and muscle relaxants had mean arterial pressure and CO after CPB and the end of surgery were higher and the need for vasopressors was significantly lower than those of total intravenous anesthesia with propofol In 2020, a meta-analytical study by Bonanni et al that randomized 42 studies in 8197 patients undergoing cardiac surgery under CPB found that after using inhalational anesthesia (sevoflurane or desfluran), cardiac index and cardiac output were elevated, reduced the need for inotropes and vasopressors compared with propofol anesthesia In summary, total anesthesia with sevoflurane has better myocardial protection and hemodynamic stability than total anesthesia with propofol 4.3.2 Evaluate some early results after surgery The study results showed that duration of mechanical ventilation, ICU stay and hospital stay, rate of postoperative complications of the two groups were not statistically significant (p > 0.05) No patient died within 30 days after surgery Our research results are similar to those of domestic and foreign authors such as Bharti et al (2008), Ho Thi Xuan Nga et al (2011), Le Huu Dat et al (2011) 2012), Jovic et al (2012),…However, Yang et al (2017) found that sevoflurane anesthesia reduced the duration of mechanical ventilation, ICU stay and hospital stay Furthermore, a meta-analysis of Bonanni et al (2020) includes 42 randomized trials involving 8197 patients undergoing open cardiac surgery under CPB found that despite rates of short-term mortality, atrial fibrillation and acute kidney injury of the sevoflurane or desflurane group were not different from those of the propofol group, but the rates of MI, mortality after year, duration of extubation, length of ICU stay and length of hospital stay of the sevoflurane or desflurane group were significantly lower than those of the propofol group 24 CONCLUSION Through the study of 56 patients undergoing open heart surgery under CPB at 108 Military Central Hospital, we draw the following conclusions: Myocardial protective effects Total inhalation anesthesia with sevoflurane has a better myocardial protective effect than total intravenous anaesthesia with propofol as shown in clinical and laboratory terms: - The heart beats faster on its own and requires less pacemaker after aortic unclamping; less need for inotropes and vasopressors with lower a proportion of required patients, number and amount of drugs with maximum VIS values within hours, 24 hours and 48 hours after surgery of 1.34 ± 2.70, 1.88 ± 3.18 and 2.23 ± 3.24 were statistically significant lower than 5.89 ± 5.74, 6.37 ± 5.73 and 6.37 ± 5.73, respectively in anaesthesia with propofol - Plasma concentrations of cardiac enzyme were statistically significant lower: Plasma concentrations of CK-MB at hours, 24 hours, 48 hours and plasma concentration of hs-troponin T at 24 hours after surgery were 55.8 ± 30.6 ng/ml, 26.8 ± 16.8 ng/ml, 6.5 ± 3.4 ng/ml and 0.88 ± 0.89 ng/ml compared with plasma concentrations of CK-MB and hs-troponin T were 74.2 ± 35.0 ng/ml, 42.1 ± 28.3 ng/ml, 9.9 ± 6.4 ng/ml and 1.54 ± 1.35 ng/ml, respectively in anaesthesia with propofol Changes in some hemodynamic indices and early results Compared with propofol anesthesia, total inhalation anesthesia with sevoflurane had less hypotension during induction of anesthesia (67.9% vs 96.4%) and had a higher ScvO2 after aortic unclamping (78.7 ± 8.5% vs ± 13.5%) but did not differ in early postoperative outcomes (duration of mechanical ventilation, length of ICU stay and length of hospital stay, rate of complications and mortality within 30 days after surgery) LIST OF PUBLISHED ARTICLE RELATING TO THESIS Vu Thanh Lam, Nguyen Quoc Kinh, Nguyen Minh Ly, et al (2022), “Comparison of the myocardial protective effect of sevoflurane versus propofol in cardiac surgery with cardiopulmonary bypass”, Journal of 108 – clinical medicine and pharmacy, 17(1), pp 126 – 132 Vu Thanh Lam, Nguyen Quoc Kinh, Nguyen Minh Ly, et al (2022), “The study on the hemodynamic effects of sevoflurane and propofol in cardiac surgery with cardiopulmonary bypass”, Journal of 108 – clinical medicine and pharmacy, 17(1), pp 114 – 120 ... beta-adrenergic antagonists, acadesine, pexelizumab, statins, etc 5 1.4 Role of sevoflurane and propofol in myocardial protection and hemodynamic effects 1.4.1 Sevoflurane Sevoflurane is an ethyl... hours, 24 hours and 48 hours after surgery of 1.34 ± 2.70, 1.88 ± 3.1 8 and 2.23 ± 3.2 4 were statistically significant lower than 5.89 ± 5.74, 6.37 ± 5.73 and 6.37 ± 5.73, respectively in anaesthesia... score after surgery *Subclinical: - Cardiac enzymes (hs-Troponin T, CK-MB, NT-proBNP), hs-CRP before and after surgery hours, 24 hours, 48 hours - Postoperative transthoracic echocardiography: EF
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